HLA class I alterations in breast carcinoma are associated with a high frequency of the loss of heterozygosity at chromosomes 6 and 15

Immunogenetics
María A GarridoNatalia Aptsiauri

Abstract

HLA class I (HLA-I) molecules play a crucial role in the presentation of tumor antigenic peptides to CD8+ T cells. Tumor HLA-I loss provides a route of immune escape from T cell-mediated killing. We analyzed HLA-I expression in 98 cryopreserved breast cancer tissues using a broad panel of anti-HLA-I antibodies. Genomic HLA-I typing was performed using DNA obtained from autologous normal breast tissue. Analysis of the loss of heterozygosity (LOH) in the HLA-I region of chromosome 6 (LOH-6) and in the β2-microglobulin (B2M) region of chromosome 15 (LOH-15) was done by microsatellite amplification of DNA isolated from microdissected tumor areas. B2M gene sequencing was done using this DNA form HLA-I-negative tumors. Immunohistological analysis revealed various types of HLA-I alterations in 79 tumors (81%), including total HLA-I loss in 53 cases (54%) and partial loss in 16 samples (14%). In 19 cases (19%), HLA-I expression was positive. Using microsatellite analysis, we detected LOH in 36 cases out of 92 evaluated (39%), including 15 samples with only LOH-6, 14 with LOH-15, and seven tumors with LOH-6 and LOH-15 at the same time. Remarkably, we detected LOH-6 in eight tumors with positive HLA-I immunolabeling. We did not find any ...Continue Reading

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Citations

Feb 15, 2020·Cancer Immunology, Immunotherapy : CII·Julia Y TsangGary M Tse
Nov 27, 2020·Journal for Immunotherapy of Cancer·Marion V GuerinNadege Bercovici
Mar 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Michael S HwangKenneth W Kinzler
Mar 27, 2021·Frontiers in Immunology·Karthik DhatchinamoorthyKenneth L Rock
Apr 4, 2021·International Journal of Molecular Sciences·Zhen ZengJames W Wells
Apr 17, 2021·Cancer Metastasis Reviews·Ignacio AlgarraAngel M Garcia-Lora
Jun 18, 2021·Frontiers in Immunology·Jonathan GoldbergJennifer L Guerriero
Jul 30, 2021·Breast Cancer Research and Treatment·Ann Hanna, Justin M Balko

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Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

SPSS Statistics
Statistical Package
Genotyper

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